DESCRIPTION: The hallucinogenic 5-.HT2A/2C agonist DOI increases expression 01 the immediate early gene c-Jbs in the corte: of the rat. This effect appears to be mediated by the 5-HT2A receptor, since the selective 5-HT2A antagonist MDL 100,90 but not the 5-HT2C antagonist SB 206553 blocks DOI-elicited Fos expression. However, cortical neurons that are 5 HT2A-like immunoreactive (-li) do not express Fos in response to DOI Instead, Fos is expressed in a band of neuron superficial to the 5-HT2A-li pyramidal cells, in register with anterogradely-labeled thalamic afferents. We also found that lesions of thalamic nuclei that project to the somatosensory cortex (SSC) attenuate DOI-elicited cortical Fos expression as does pretreatment with an AMPA/KA antagonist. My thesis will determine if DOI acts at thalamic or cortical 5-HT2 receptors to induce Fos and to assess the role of glutamate release in DOI-elicited Fos expression. In order to determine if DOI acts on 5-HT2A receptors in the thalamus, the impact of intra-thalamic DOI administration on cortica Fos expression will be examined. Conversely, the effect of intra-thalamic administration of MDL 100,907 on the ability of systemic DOI to induce Fos will be determined. In order to assess if DOI causes an increase in extracellular glutamate release (consistent with the glutamatergic nature of thalamocortical neurons), in vivo microdialysis will be used to measure extracellular glutamate levels in response to systemic, intra-thalamic or intra-cortical DOI administration Finally, I will determine if those neurons that express Fos in response to DOI can be characterized by the presence of particular glutamate receptor subunits.